Borrelia burgdorferi, the infectious agent of Lyme disease, is transmitted to mammals through the bite of infected Ixodes ticks. During transmission, B. burgdorferi must recognize and adapt to changes in the environment. Bacterial oligopeptide permeases, five membrane-associated proteins belonging to the ABC transporter family, provide a mechanism for the uptake of small peptides, which not only provide nutrients but often serve as environmental signals that lead to a variety of adaptive responses. We speculate that in B. burgdorferi oligopeptide permease may be involved in sensing and signaling a response to the changing conditions that accompany transmission between ticks and mammals. To investigate this possibility, we have identified and characterized a chromosomal locus that encodes homologs of all five components, as well as two plasmid-encoded components. We have examined gene expression of the oligopeptide components at temperatures that mimic ticks and mammals. We have also undertaken genetic studies to aid in determining the physiological role that oligopeptide permease plays in the natural infectious cycle of B. burgdorferi.